tbuckley/cabot-search huggingface dataset:
BRCANet: A deep hybrid network in predicting BRCA1/2 gene mutation of breast cancer with dynamic contrast-enhanced breast MRI.
Authors: Wen-Ming Cao, Xiaojia Wang, Jian Liu, Lili Wang, Xiaodong Zhang, Jiani Pan, Weiwu Ye, Zhanhong Chen, Yabing Zheng, Xiying Shao, Yuanji Xu
Journal: Journal of Clinical Oncology (2022)

e13576 Background: BRCA1/BRCA2, representing as an important genetic biomarker of breast cancer (BCA), can provide clinically significant implications for personalized risk assessment, effective treatment option, and prognostic prediction. Methods: We here proposed the BRCANet, a novel end-to-end convolutional neural network for noninvasively determining BRCA1/BRCA2 mutation by integrating clinical, radiomics and deep learning of dynamic contrast-enhanced (DCE) MRI. BRCANet accepts different forms of medical data including clinicopathologic identifications, high throughput radiomics and deep imaging features of breast MRI using a deep hybrid neural network for data/feature integration. Model training and cross-validation was performed in 132 case-controlled BCA patients from two in two tertiary care hospitals, in which clinicopathologic, genomic and image data of BCA lesions were available and center-standardized for study analysis. Results: Results show that a BRCANet-Plus model, embedded with clinicopathologic, radiomics and deep MRI features achieves an arear under curve of (0.783; 95% confidence intervals [CIs], 0.704 - 0.848) for predicting BRCA1/2 mutation, outperforming the compared state-of-the-art methods, i.e., BRCANet derived from image-only data (0.743; 95% CIs, 0.659 - 0.815; p = 0.037), and BRCARad derived from radiomics-only data (0.734; 95% CIs, 0.649-0.807; p = 0.031). After net benefit evaluation, the proposed BRCANet-Plus shows promise to improve diagnostic performance against conventional clinical or image approaches. Conclusions: Therefore, we concluded the presented deep hybrid approach by integrating multimodal clinical-imaging data, especially breast MRI, have a great potential to predict BRCA1/2 mutational status of BCA. This proof-of-concept strategy can be utilized for studying similar clinical questions.
The Ethics of Access: Reframing the Need for Abortion Care as a Health Disparity
Authors: Katie Watson
Journal: The American Journal of Bioethics (2022)

The majority of U.S. abortion patients are poor women, and Black and Hispanic women. Therefore, this article encourages bioethicists and equity advocates to consider whether the need for abortion care should be considered a health disparity, and if yes, whether framing it this way would increase the ability of poor women and women of color to get the medical care they need. In order to engage with these critical questions, bioethicists must avoid abortion exceptionalism and respect patients as moral agents. Centering the conscience of pregnant people shifts our analysis away from the ethics of the act of abortion, and toward the ethics of access to abortion care. Because the Supreme Court is on the brink of shifting the question of abortion's legality to state legislatures, this is the moment for all bioethicists to clarify and strengthen their thinking, writing, and teaching in abortion ethics.
Comparison between long-term outcomes of low-dose-rate brachytherapy and radical prostatectomy in patients with intermediate-risk prostate cancer: Propensity match scoring analysis
Authors: F. Urabe, T. Kimura, H. Sasaki, K. Iwatani, K. Aikawa, K. Tashiro, Y. Tsutsumi, M. Morikawa, S. Sato, H. Takahashi, M. Aoki, K. Miki, S. Egawa
Journal: European Urology (2022)
68Ga-DOTA-FAPI-04 PET/CT Imaging of Tracheal Mucoepidermoid Carcinoma
Authors: Dengsai Peng, Qian Chen, Jianpeng Cao, Yilin Huang, Yue Chen
Journal: Clinical Nuclear Medicine (2022)

A 23-year-old woman presented with a dry cough and dyspnea. Contrast-enhanced CT revealed an intratracheal space-occupying lesion with continuous homogeneous enhancement and airway stenosis. The patient then underwent 68 Ga-DOTA-FAPI-04 PET/CT, which showed increased uptake of FAPI-04 by the lesion. Postoperative pathology confirmed the lesion as tracheal mucoepidermoid carcinoma. This case reports a rare site of mucoepidermoid carcinoma and highlights the potential utility of 68 Ga-DOTA-FAPI-04 PET/CT for the diagnosis of tracheal mucoepidermoid carcinoma.
Gender features of the chronic pain effect on some vascular endothelial growth factors and their skin receptors on the B16/F10 melanoma model.
Authors: Inga Movlievna Kotieva, Elena M. Frantsiyants
Journal: Journal of Clinical Oncology (2022)

e24061 Background: Patients with oncological pathology, especially with the progression of the disease, often have chronic pain[1]. Pain effects singly can cause dysfunction of the vascular system, which could be an additional risk of the tumor process progression. The aim of the study was to identify gender-specific chronic pain effects on some vascular endothelial growth factors and their skin receptors in the B16/F10 melanoma model. Methods: The study was conducted on mice of the C57BL/6 line (females, males; age 8 weeks, weight 21-22 g, n = 48, 12 animals in each group). Two weeks after the ligation of the sciatic nerve melanoma B16/F10 was transplanted under the skin in the back of the main groups of animals (I- females, II-males); control groups were held the same procedure without ligation (III-females, IV-males). The levels of VEGFA, sVEGFR1, VEGFC, sVEGFR3 were determined in intact skin by ELISA. All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Results: Chronic pain contributed to the accumulation of VEGF-A, sVEGF-R1, VEGF-C in the skin and the reduction of sVEGF-R3 in all animals: in females - 2.7 times, 2.9 times, 6.1 times and 6.1 times, accordingly, in males - 3.1 times, 3.7 times, 3.5 times and 7.2 times, accordingly. Consequently, in males the amplitude of fluctuations of VEGF and their receptors in the skin against the background of pain was higher than in females, except for VEGF-C, the amount of which increased in females more than in males, despite its identical initial level in the skin of animals of both sexes. As a result, the skin of males with pain contained more VEGF-A, sVEGF-R1 and sVEGF-R3, accordingly, by 1.4 times (p &lt; 0.05), 2.0 times and 1.9 times (p &lt; 0.05) and less VEGF-C - by 1.8 times (p &lt; 0.05). Conclusions: Chronic neuropathic pain had different effects on changes in the level of vascular endothelial growth factors and their receptors in intact skin in females and males of melanoma B16/F10 tumor carriers. The gender characteristics of the effect of chronic pain on neoangiogenesis may be associated with different rates of growth and development of the malignant process in male and female mice in the experiment. References [1] Kotieva I.M. et al. Chronic pain and accumulation of growth factors in perifocal tissues of melanoma and impact on malignancy and early metastasis. Journal of Clinical Oncology . 2018. Т. 36. № S15. С. e21621.
Prognostic analysis of doublet agent concurrent chemoradiotherapy in locally advanced cervical cancer: A propensity score analysis.
Authors: Jingjing Wang, Minjie Shan, Yeqian Feng, Jinlei Wang, Lin Wu, Xianling Liu, Wen Zou
Journal: Journal of Clinical Oncology (2022)

e17514 Background: Platinum-based concurrent chemoradiotherapy (CCRT) is the current standard treatment for patients with locally advanced cervical cancer (LACC). Previous reports showed that doublet agent CCRT can provide better prognosis than single agent CCRT. However, several controversies surround the doublet agent regimen. This retrospective study compared the efficacy and safety of cisplatin and nedaplatin in doublet agent CCRT by propensity score (PS) matching. Methods: Information on patients with stage IIB-IIIC2 cervical cancer who received doublet agent CCRT from January 2015 to December 2020 were collected. The chemotherapy regimen was docetaxel (75mg/m 2 ) combined with carboplatin (AUC = 4-5) / cisplatin (50–70mg/m 2 ) / nedaplatin (50-75mg/m2) once every 3 weeks. All patients underwent external-beam radiotherapy with intensity-modulated radiotherapy at a dose of 45–50 Gy/25fx to the pelvis with or without involving the para-aortic region and 60 Gy/25fx to gross disease in the lymph nodes, and 2-dimensional intracavitary brachytherapy with dose of 30 Gy/5fx to point A. Patients were classified into the cisplatin group and nedaplatin group. Treatment outcomes were compared between the two groups after 1:1 ratio PS matching adjusted for age, BMI, FIGO stage, pathology, tumor diameter, differentiation, complication, and cycles of chemotherapy. Categorical variables were compared using the χ 2 test or Fisher's exact test. Clinical outcomes were analyzed using the Kaplan–Meier method with log-rank test. Results: There are 295 patients enrolled, median age 55 years (32–73 years). The median follow-up time was 38 months (5–77 months). The median number of chemotherapy cycle is 4 (1–6 cycles). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 82.5% and 80.4%, respectively. After PS matching, there were 83 patients each in the nedaplatin group and cisplatin group. All background factors between the two groups were well-balanced. There was no significant difference between the cisplatin and nedaplatin groups in terms of objective response rate (97.6% and 98.8%, p = 0.212), 5-year OS rate (96.5 vs.69.8, p = 0.066), and PFS rate (90.8 vs.72.4, p = 0.166). Also, there was no significant difference between the cisplatin and nedaplatin groups in terms of hematological toxicity (36.1% vs. 28.9%, p = 0.408), nausea and vomiting (19.3% vs. 20.4, p = 0.874), radiation proctitis (25.3% vs. 14.5%, p = 0.535), and radiation proctitis (12% vs.9.6%, p = 0.212). Conclusions: Doublet agent concurrent chemoradiotherapy is feasible, safe, and shows high efficacy in LACC patients. Here, the cisplatin group and nedaplatin group have similar prognosis and side effects, suggesting that nedaplatin and cisplatin are equivalent and can be replaced with each other for concurrent doublet agent CCRT.
Use of real-world data (RWD) to assess the utility of cell-free circulating tumor DNA (cfDNA) in identifying resistance to early treatment in advanced breast cancer (aBC).
Authors: Seth Andrew Wander, Caroline Weipert, Jiemin Liao, Nicole Zhang, Pedram Razavi
Journal: Journal of Clinical Oncology (2022)

1011 Background: The approvals of CDK4/6 inhibitors (CDK4/6i) and alpelisib (a PI3Ka inhibitor, PI3Ki) have overhauled early treatment of hormone positive aBC. While some clinical trials have investigated mechanisms of resistance to these drugs, their impact on tumor evolution requires further exploration. Here we use cfDNA to examine molecular changes pre- and post-CDK4/6i or PI3Ki treatment and use RWD to assess the impact of putative resistance alterations on response to treatment. Methods: Patients (pts) with aBC were identified via the Guardant INFORM database and included if they had a cfDNA test within 90 days prior to therapy initiation and/or 90 days after therapy discontinuation with CDK4/6i or PI3Ki. Pts with RB1 loss of function (LOF) alterations (alts) who received CDK4/6i and pts with PTEN LOF alts who received PI3Ki were separately identified, and these cohorts were matched 1:3 with a RB1/PTEN negative population respectively, by age (+/- 5 years), sex, year of cfDNA test, and line of therapy. Log-rank tests were used to assess differences in time to discontinuation (TTD) and time to next treatment (TTNT). Results: Differences in the frequencies of certain alts detected in pts pre- and post-CDK4/6i or PI3Ki treatment are shown (Table). Pts with RB1 LOF alts prior to the start of CDK4/6i had significantly worse TTD and numerically worse TTNT versus controls (TTD = 3 mos vs 4.7 mos, p=0.018; TTNT = 7.3 mos vs 8 mos, p=0.082). Pts with PTEN LOF alts prior to start of PI3Ki had no significant difference in TTD or TTNT versus controls (TTD = 4.1 mos vs 4.1 mos, p=0.92; TTNT = 7.4 mos vs 7 mos, p=0.32). Notably, 54% of pts receiving CDK4/6i and 84% of pts receiving PI3Ki were on their third or later line of therapy. Conclusions: Using cfDNA, we were able to further characterize the resistance landscape of both CDK4/6i and PI3Ki, and identified specific ESR1, RB1 and PTEN alterations that appear likely to occur under the pressure of therapy. Our real-world analysis examining RB1 LOF alts added further evidence to suggest it may be both a primary and acquired resistance mechanism to CDK4/6i. As a non-invasive alternative to tissue biopsies, this data further illustrates that cfDNA can provide unique insight into tumor evolution and disease progression in the aBC setting. [Table: see text]
Malnutrition screening in cancer patients on chemotherapy.
Authors: Sindusha R Gudipally, Ala'a Tayyem, Rohit Venkatesan, Maurice Willis
Journal: Journal of Clinical Oncology (2022)

e18640 Background: Malnutrition occurs in 40-80% of cancer patients and has great impact on quality of life and treatment outcomes. The essential elements of malnutrition for patients with cancer are early identification of patients at greatest risk, nutrition assessment to determine the level of deficit, and appropriate nutrition intervention. Currently we don’t have a standard tool to identify patients who are malnourished on chemotherapy and nutrition referrals were placed based on provider's subjective assessment. Methods: From March 2020 to August 2020, 41 patients on chemotherapy were reviewed, of which 29% were referred to nutrition. To assess the patients at risk early on, a validated Malnutrition Screening Tool(MST) was implemented from September 2020 to February 2021 in the Medical Oncology fellow's clinic notes. Although the original MST was implemented mostly for inpatient elderly patient population, the idea of this study was to apply this tool to assess acute nutrition issues for patients receiving cancer therapy in the outpatient setting. This tool used two simple questions, Have you lost weight recently without trying? (If lost 1-6lbs = 1points, 7-13lbs = 2points and &gt; 13 = 3points), and have you been eating poorly because of decreased appetite? (Yes = 1 point; No = 0 points).A smart phrase which included these questions was used in the notes and if patients scored greater than or equal to 2, were considered malnourished and qualified for nutrition referrals. Other variables included were age, sex, and type of cancer. Results: Of the 41 charts that implemented MST, 21 patients(49%) screened positive and all 100% of them were referred to nutrition. After implementing this tool, there was a 20% increase in identifying and referring the malnourished patients who were receiving cancer therapy during the clinic visits. Median age for patients who screened positive was 60 years, more males screened positive than females(60% vs 40%). Gastro-intestinal malignancies and head and neck cancers were the highest who screened positive in the MST group(14% each out of the 49%). Conclusions: Malnutrition is a major cause of morbidity and mortality in patients with any stage cancer and especially worse in advanced stage cancer. By simply using this two-step questionnaire, we were able to identify 20% more patients who were at risk for malnutrition. Older age, Males and Gastro-intestinal and Head and Neck cancer patients are more at risk and needs to be more closely screened. The study concludes that using a simple tool in the outpatient clinics can assess patient's at risk and provide early qualitative support throughout course of therapy.
HGG-52. Combinatorial modulation of hypoxic pathways leads to anti-tumoral effects in H3.3 K27M midline gliomas
Authors: Quentin Fuchs, Benoit Lhermitte, Sophie Foppolo, Clemence Hubsch, Sophie Martin, Monique Dontenwill, Natacha Entz-Werlé
Journal: Neuro-Oncology (2022)

Abstract Pediatric midline high-grade gliomas (pmHGG) are aggressive and incurable tumors of the central nervous system. There is a pressing need for novel therapeutic approaches to treat them. Therefore, proactive translational studies wish to go further discovering new targetable proteins and pathways. Our objectives are then to focus on the modulation of microenvironmental extrinsic features like intra-tumor hypoxia. To do so, we looked first on expressions of hypoxia biomarkers in a pool of patient-derived preclinical models of pmHGG and tested oxygen modulations, as well as hypoxia drug targeting. We designed subsequently our work in those models H3.3 mutated to evaluate balance between HIF1 and HIF2 expressions (immunofluorescence, RTqPCR, RNAseq and metabolomics) and to evidence the impact of hypoxia targeting combined to irradiation on cell proliferation, migration and metabolism. Hypoxia is inducing mainly HIF1 expression and its upstream and downstream pathways and is stabilizing HIF2 expression. Both HIFs are part of crucial survival signaling and represent targets to combine with irradiation. The use of their specific inhibitors shows an antiproliferative effect when HIF1 is downregulated. HIF2 inhibitors are stopping HIF2 transcriptional effect letting us uncover new pathways that this hypoxic inducible factor is regulating in pmHGG (stemness, glycolytic and aminoacid metabolism and histone expression). Together with irradiation this anti-hypoxic strategy seems to be highly effective on cell arrest and migration. Those results are confirming central roles of HIFs in pmHGG and their potencies in pmHGG therapies. The therapeutic efficiency is independent from p53 abnormalities in our models.
Inflammatory mediators to predict left adverse ventricular remodelling in revascularized STEMI patients
Authors: E Bevilacqua, I Galeano-Otero, FJ Guerrero-Marquez, D Falcon- Boyano, G Baron-Esquivias, T Smani, A Ordonez-Fernandez, R Del Toro
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Institute of Carlos III the Spanish Ministry of Economy and Competitiveness Background Primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) improves the survival of patients. Nevertheless, some patients develop left ventricular adverse remodeling (LVAR). The main objective of this study is to find reliable prognostic biomarkers for patients developing LVAR, focusing in the role of pro-inflammatory mediators, including cell populations and secreted molecules. Methods We assessed the level of pro-inflammatory cell subsets, before and after the revascularization, 1 and 6 months after the PPCI, using flow cytometry. We also performed miRNAs microarray in isolated peripheral blood mononuclear cells (PBMCs), and examined the levels of 27 cytokines in patients’ serum by multiplex ELISA. Results We observed that levels of pro-inflammatory monocytes were increased soon after PPCI, in patients who afterward developed LVAR. Furthermore, we detected significant increase in the concentration of secreted cytokines such as IL-1b, IL-17, IFN-g and VEGF in LVAR patients post-PPCI. Moreover, specific miRNAs levels regulating these cytokines secretion, also correlated with LVAR. Multivariate regression analysis and ROC curves indicated that these inflammatory mediators were good biomarkers to correlate with the appearance of LVAR in patients. In addition, we found that the combined analysis of these biomarkers increased the specificity and sensibility to identify patients with LVAR. Conclusion Our data suggest that the combined analysis of these inflammatory axes and related molecules, could reliably predict LVAR in STEMI patients.
Desmopressin is twice effective in females: A systematic review and meta-analysis on medical treatment of nocturia
Authors: H. Mostafaei, K. Mori, B. Pradere, T. Kawada, R. Sari Motlagh, T. Yanagisawa, F. Quhal, E. Laukhtina, P. Rajwa, A. Aydh, F. König, M. Pallauf, H. Salehi-Pourmehr, S. Hajebrahimi, S.F. Shariat
Journal: European Urology (2022)
Sintilimab plus anlotinib as second or further-line therapy for small cell lung cancer: An objective performance trial.
Authors: Shuxiang Ma, Zhen He, Lili Wang, Yufeng Wu, Sen Yang, Haiyang Chen, Yingxi Wu, Yuqing Mo, Yang Liu, Qiming Wang
Journal: Journal of Clinical Oncology (2022)

8516 Background: Small cell lung cancer (SCLC) tends to progress rapidly on first-line therapies, with limited subsequent-line treatment options. Methods: In this single-arm objective performance trial, adult patients with extensive-disease SCLC (ED-SCLC) received intravenous sintilimab 200 mg on day 1 and oral anlotinib 12 mg on days 1-14. Treatment lasted for 3 weeks per cycle and was continued until disease progression, unacceptable toxicities, or death. The primary endpoint was the superiority of progression-free survival (PFS) versus a PFS of 2.8 months with historical topotecan control. Results: Forty-two patients were enrolled, and 39 patients were evaluable for efficacy. Twenty-six patients (66.7%) had ED-SCLC, and 13 (33.3%) relapsed after concurrent chemoradiotherapy. The median follow-up was 11.9 months. The median PFS was 6.0 months (95%CI: 4.8-7.2). The 6- and 12-month PFS rate was 50.5% and 27.8%, respectively. Fourteen patients died by the data cut-off date, and overall survival (OS) was immature (16.1 months, 95%CI: 9.4-22.7). The 12- and 18-month OS rate was 56.7% and 42.5%, respectively. Three patients attained complete response and 16 achieved partial response, and 12 patients had stable disease; the objective response rate was 48.7% and the disease control rate was 79.5%. Forty patients (95.2%) had at least one treatment-related adverse event (TRAE). The most frequent TRAEs were hypothyroidism (45.2%), hypoproteinemia (40.5%) and elevated gamma-glutamyl transpeptidase (38.1%). Conclusions: Immunotherapy with sintilimab plus antiangiogenic drug anlotinib demonstrated promising antitumor activities as second or further-line therapy for ED-SCLC and had manageable toxicities. The findings support further development of this combination regimen for ED-SCLC. Clinical trial information: NCT04055792.
MEDB-21. SOX2+ cells: the perpetrators of medulloblastoma relapse
Authors: Marzena Swiderska-Syn, Julia Mir-Pedrol, Jezabel Rodriguez-Blanco
Journal: Neuro-Oncology (2022)

Abstract Pediatric brain tumors are the number one cause of cancer-related death in children, with medulloblastoma being the most common type. While survival in patients with medulloblastoma has dramatically improved since chemotherapy was added to standard of care protocols, still 30% of tumors will recur. As recurrent disease in medulloblastoma patients in considered uniformly lethal, it is key to identify the cells allowing tumor relapse, and their targetable regulators. By analyzing single cell transcriptomic data, we uncovered a population of SOX2 labeled astrocyte like cells resistant to SMO inhibitors in clinical trials. Using SOX2-enriched medulloblastoma cultures, we observed that SOX2+ cells rely on non-canonical GLI signaling to propagate medulloblastoma. Therefore, in vivo inhibition of SHH signaling using functionally different GLI inhibitors depleted the SOX2+ cell pool, what led to less aggressive tumors that lacked the ability to further engraft. Stressing the translational relevance of our findings, a clinically relevant GLI inhibitor not only exhausted SOX2+ cells driving tumor relapse, but increased overall survival in mice harboring medulloblastoma. Our results emphasize the importance of using targeted therapies that deplete SOX2+ cells to prevent medulloblastoma recurrence.
Ureteral stent encrustation: Evaluation of forgotten encrustation calcification score, kidney ureter bladder score and encrustation burden score as predictors of a complex surgery
Authors: A. Nacchia, A. Franco, L.M. Rovesti, R. Lombardo, A.M. Cicione, P. Spatafora, L. Verdelli, M. Gacci, Y. Al Salhi, A. Fuschi, F. Sommatino, A. Simonato, A.L. Pastore, S. Serni, A. Carbone, A. Tubaro, C. De Nunzio
Journal: European Urology (2022)